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Abstract:

The invention relates to a wound closure material with a core of
biodegradable material, wherein at least one side, preferably two sides
of the core of biodegradable material are provided with at least one,
preferably a multitude of discrete spots of an adhesive. As with more
common wound closure techniques like sutures, clips and tapes applied
over the wound, new tissue has to close a gap between the wound edges.
Use of a wound closing material of the present invention does not only
have the advantage of a secure physical connection between the edges, but
the material serves as scaffolding for the new tissue. It may also serve
the cells as artificial extracellular matrix they can adhere to.

Claims:

1. Wound closure material with a core of biodegradable material, wherein
at least one side of the core of biodegradable material is provided with
a multitude of discrete spots of an adhesive and the core of
biodegradable material comprises an open cell structure.

2. Wound closure material according to claim 1, wherein at least two
opposing sides of the core of biodegradable material are provided with a
multitude of discrete spots of an adhesive.

3. Wound closure material according to claim 1, wherein the core of
biodegradable material comprises at least a polyurethane foam with open
pores and/or a web of non-woven material.

4. Wound closure material according to claim 1, wherein the core of
biodegradable material is provided as an area-measured material selected
from the group consisting of pads, tapes, strips, polygonal sheets,
rectangular sheets and circular sheets.

5. Wound closure material according to claim 1, wherein the discrete
adhesive spots are provided as lines, dots or in a polygonal or circular
shape.

6. Wound closure material according to claim 1, wherein the discrete
spots have a dimension of 0.5 mm-5 mm.

7. Wound closure material according to claim 1, wherein the discrete
spots each have a surface between 0.2 mm2 and 20 mm.sup.2.

8. Wound closure material according to claim 1, wherein the discrete
adhesive spots are evenly spread over the entire area of the at least one
side of the core of biodegradable material.

9. Wound closure material according to claim 8, wherein at least 30% of
the at least one side of the core of biodegradable material is not
covered by the discrete spots of adhesive.

10. Wound closure material according to claim 1, wherein the adhesive of
the adhesive spots has an adhesive strength to human tissue of between
0.04 to 6 MPa.

11. Wound closure material according to claim 1, wherein the adhesive is
selected from the group consisting of moisture curing polyurethanes,
pressure sensitive adhesives, adhesives based on polysaccharides, and
adhesives based on polymers which are activated by water.

12. Wound closure material according to claim 1, wherein the adhesive is
selected from the group consisting of adhesives from biological sources,
hybrid adhesives having a synthetic backbone, and biomimetic adhesive
sites.

13. Wound closure material according to any of claim 1, wherein the at
least one side of the core of biodegradable material provided with the
multitude of discrete spots of an adhesive is protected from the
environment before use.

14. Method of production of a wound closure material comprising the steps
of: (a) providing a core of a biodegradable material having an open cell
structure; (b) applying a multitude of spots of an adhesive to at least
one side of the core of biodegradable material.

15. Method of closing a wound comprising the steps of: (a) applying a
wound closure material according to claim 1 to a wound in such a way that
the at least two opposing sides provided with the multitude of discrete
spots of an adhesive face at least two wound edges; (b) pressing the at
least two wound edges together with the wound closure material in between
the edges; and (c) allowing the adhesive to cure so that the wound edges
attach to the wound closure material.

16. (canceled)

17. The method according to claim 15 wherein the wound is closed after
surgical transection.

Description:

[0001] The present invention relates to a wound closure material with a
core of biodegradable material provided on at least one side with at
least one, but preferably a multitude of adhesive spots, a method of
production of such a wound closure material, use of such a wound closure
material and a method to close a wound. Since the closure material is
biodegradable, a wound may be closed without the need to remove the
material once wound healing is completed.

[0002] Small wounds may simply be protected by applying a wound cover such
as an adhesive plaster or gauze on top of the wound. Closure of the wound
will then occur by natural wound closing mechanisms. Bigger wounds
stemming from injuries or from surgical interventions have to be closed
and the wound edges physically held together. Traditionally this is being
done by classical surgical sutures. Another possibility is to use suture
clips. Sutures and clips may both be made from biodegradable material,
thus eliminating the need of removing them after completion of wound
healing. Another alternative is the use of a strong adhesive tape applied
over the wound to hold the edges of the wound together.

[0003] Throughout the history of medicine, different adhesive materials
were tested as wound closure material. Early attempts used herbal
adhesives, such as resins, or mixtures of different animal, plant and
mineral material to glue the wound edges together.

[0004] Today, even though adhesives are of increasing importance in most
fields of technology, such as transportation, construction, etc., there
are only very few adhesives used in medicine. Almost 90% of all medicinal
adhesives are used in topical applications in the form of patches, wound
dressings or as structural dental adhesives and fillings.

[0005] Topical tissues, by definition, are exposed to the outside world
and are `dry` so that their moisture content correlates with the ambient
humidity. The cells of topical tissues often are `dead` in the sense that
they no longer have a metabolism. Adhesives for topical applications need
to have adhesive strengths to match their respective purpose. Moreover,
they must cope with some body fluids like sweat or sebum. Additionally
they must not emit toxic chemicals or chemicals which could interfere
with the healing process of the body.

[0006] Adhesives to be used inside the body have to cope with an almost
completely fluid environment, as the surfaces to be bound are immersed in
blood and other body fluids. Applications of such adhesives have hitherto
been proposed, but they are, on closer examination, scarce and restricted
to very few systems such as alkyl-cyanoacrylates or fibrin.

[0007] Adhesives based on fibrin technology show a reasonable
biocompatibility but low bond strength. This is prohibitive for their use
in most load bearing applications, e.g. wounds where tension might occur.
Additionally, they are very expensive since their biological origin
requires extensive purification in order to avoid microbiological or
allergenic contaminants.

[0008] Cyanoacrylate-based adhesives are reported to strongly interfere
with the natural healing process. Moreover, there is toxicological
concern with respect to the degradation products of some of these
formulations.

[0009] Other adhesives, e.g. based on polyurethanes or epoxy resins, show
excessive heat formation upon curing which has negative effects on wound
healing and might even lead to tissue necrosis.

[0010] Another drawback with the known systems is that the adhesives have
to be applied over a large area of the tissues, such that the adhesive
subsequently acts as a barrier hindering the growth of new tissue within
the wound, thus considerably interfering with the healing process.

[0011] It is an objective of the present invention to avoid the
disadvantages known from prior art and to provide for a wound filling
material showing beneficial effects on wound healing. This objective is
achieved with a wound closure material according to claim 1.

[0012] A wound closure material according to the present invention has a
core of biodegradable material which comprises an open cell structure. At
least one side, but preferably two sides of said core of biodegradable
material are provided with at least one, but preferably a multitude of
discrete spots of an adhesive.

[0013] Biodegradable material as understood herein means a material which
is over time completely disintegrated and resorbed by the body. This
disintegration may be due to hydrolysis, oxidation or enzymatic cleavage.
It is understood that a biodegradable material and none of its
degradation should not be toxic to the organism, even at higher
concentrations which may occur at the site of application. Moreover, such
a material should preferably also not be allergenic. Use of a
biodegradable material has the advantage that the wound closure material
does not need to be removed but will gradually be replaced by new tissue.

[0014] At least one side of the core of the wound closure material is
provided with at least one, but preferably a multitude of discrete spots
of an adhesive. Preferably, at least two opposing sides of the core are
provided with the at least one, but preferably the multitude of discrete
spots of an adhesive.

[0015] A spot as understood herein is a small area of finite dimensions,
without any restriction as to its shape or position. Therefore, a
multitude of discrete spots is understood as to mean several spots having
no direct connection with each other.

[0016] Having at least one, but preferably a multitude of discrete spots
of an adhesive on at least one side of the core of biodegradable material
has the advantage that the adhesive does not cover the entire surface of
the at least one side, therefore leaving space for cells to grow directly
onto and/or into the surface of the core. This facilitates degradation of
the core as well as the ingrowth of new tissue cells into it.

[0017] The adhesive used to apply the spots has to be biocompatible and
non-toxic. Preferably the adhesive is also biodegradable. Most preferably
the degradation rate of the adhesive is slower as the degradation rate of
the biodegradable material used for the core.

[0018] Having adhesive on at least one side of the core allows attaching
the wound closure material into a wound and/or between edges of a wound.

[0019] The core of biodegradable material comprises an open cell
structure. Open cells are understood to be voids within the material
which are in fluid connection with each other. These cells may be for
example pores, channels and the like. This has the advantage that the
core may be moistened by body fluids and that tissue cells can grow into
said pores, thus gradually replacing the material of the core with new
tissue. This has considerable beneficial effect on the rate of wound
healing.

[0020] In a preferred embodiment of the present invention at least two
opposing sides of the core of biodegradable material are provided with at
least one, but preferably a multitude of discrete spots of an adhesive.
This has the advantage that the material can be used to close a wound by
first adhering a first edge of the wound to a first side of the core and
then subsequently adhering a second edge of the wound to the opposite
side of the core, thereby tightly closing the wound. It is understood
that more than one or two sides of the core may be provided with the at
least one or multitude of discrete adhesive spots.

[0021] With the more `classical` wound closure techniques like sutures,
clips and tapes applied over the wound, new tissue has to close a gap
between the wound edges. Use of a wound closing material of the present
invention does not only have the advantage of a secure physical
connection between the edges, but the material serves as scaffolding for
the new tissue. It may also serve the cells as artificial extracellular
matrix they can adhere to.

[0022] Preferably, the core of biodegradable material comprises at least a
polyurethane foam with open pores. Biodegradable polyurethane foams are
known in the art. Especially suitable polyurethane foams to be used in
the present invention are for example described in European patent
application EP 09167043.0 which is incorporated herein by reference in
its entirety. The pores of the foam preferably have a largest diameter in
the range of between 100 μm and 400 μm, most preferably between 100
μm and 250 μm. Alternatively, the core may comprise a web of
non-woven material, preferably a silica gel fibre fleece. As understood
herein, non woven material is a fabric-like material made from long
fibres, bonded together by chemical, mechanical, heat or solvent
treatment. Biodegradable non-woven materials are known in the field.
Especially preferred a fibre fleece made of silica gel is used. Such a
fleece has a multitude of open cells and is slowly degraded in the body
while showing sufficient strength to be used as wound closing material.

[0023] Generally, the biodegradation rate of the core material should be
in the range of 1 to 4 weeks such as to serve for ingrowth of cells and
formation of new tissue. The degradation rate should be chosen according
on the tissue the wound closure material is used in and the condition of
the wound.

[0024] The core of biodegradable material is preferably provided as an
area-measured material, preferably as a pad, tape, strip or polygonal
sheet, most preferably in the form of a rectangular or circular sheet.
This offers the advantage that the wound closure can be used to stick
edges of a wound together. Moreover, such shapes may easily be cut and
adapted to any wound size and shape by medical personal. Especially
preferred is a core in the form of a tape roll which may be cut in an
appropriate length prior to use. Such tapes might be provided in
different widths and thicknesses.

[0025] The discrete adhesive spots are preferably provided as lines, dots
or in a polygonal or circular shape on the at least one side of the core.
The adhesive may be provided as lines of different length and width on
the at least one side of the core. Alternatively, the adhesive may be
provided as dots. Such dots are generally of circular shape and may have
different diameters. Alternatively, the spots may be provided in any
circular or polygonal shape. This includes rectangular, trapezoidal,
triangular, round and oval shapes of any suitable dimension. The spots
may all be provided in the same shape on the at least one side.
Alternatively, the spots may be provided in different shapes. All shapes
provided on the at least one side may have the same dimension and/or
surface area. Alternatively, the shapes may be of different dimensions
and/or surface areas.

[0026] Preferably, the discrete spots are, in first approximation, of
circular shape with a diameter between 0.5 mm-5 mm, preferably 0.6 mm-2.5
mm. The number of spots per side is chosen such as to maximize the area
uncoated by the adhesive while simultaneously providing enough bond
strength to stabilize the closure of the wound, i.e. resist the external
forces affecting the wound. This ensures that a maximum of unobstructed
tissue is available for the growth of new cells.

[0027] The discrete spots may each have a surface between 0.2 mm2 and
20 mm2, preferably between 0.5 mm2 and 5 mm2. Spots with a
surface in this area have sufficient adhesive strength while still being
small enough such as not to cover too much of the surface.

[0028] Preferably, the discrete adhesive spots are evenly spread over the
entire area of the at least one side of the core of biodegradable
material. This allows for an optimal distribution of tensile stress over
the entire surface of the core side. Moreover, this allows for an optimal
adherence of the wound filling material to the wound edges, which has a
beneficial effect on the ingrowth of cells into the core.

[0029] Further, at least 30%, preferably at least 60%, most preferably at
least 90% of the at least one side of the core of biodegradable material
is not covered by the discrete spots of adhesive. This allows optimal
growth of cells onto and/or into the core of biodegradable material. If
too much of the surface of the side is covered with the adhesive, tissue
cells will be hindered to grow onto and/or into the core of biodegradable
material. If a too small amount of the surface is covered with the
adhesive, only pore adhesion of the wound closure material to the wound
edges will be achieved.

[0030] Preferably the adhesive spots are provided on the at least one side
of the core of biodegradable material in a regular pattern. As an
example, all spots may be provided such as to be regularly spaced apart
from their neighbouring spots. Alternatively, the spots may be provided
such as to generally define a geometrical pattern on the side.
Alternatively, the adhesive spots are provided on the at least one side
of the core of biodegradable material in a random pattern.

[0031] The adhesive of the adhesive spots should have an adhesive strength
of between 0.05 to 20 MPa, preferably of between 0.1 to 10 MPa. The
typical tensile strength of connective tissue, for example skin, is in
the range of 0.01 to 8 MPa. It has to be taken into consideration that
the spotty pattern of the adhesive reduces the total adhesive force by
the ratio between the total surface and the sum of the surfaces of the
spots within the surface.

[0032] Preferably the adhesive comprises a moisture curing polyurethane.
The moisture curing polyurethane is preferably composed of an
isocyanate-terminated polyesterpolyol pre-polymer or an
isocyanate-terminated polyetherpolyol pre-polymer. Further the adhesive
may also comprise a pressure sensitive adhesive. Preferably, the pressure
sensitive adhesive has an increased stick in wet environments. Such
adhesive are known in the art. The US2006/211808 exemplary describes a
composition for pressure sensitive adhesives with an improved wet stick.
Further, the adhesive may be based on polysaccharides such as alginates,
pectins, polysaccharide gums, and other similar systems as well as on
polymers which are activated by water such as gum arabic, polyvinyl
pyrrolidone, polyvinylalcohol and other similar systems.

[0033] Alternatively, the adhesive comprises at least an adhesive from a
biological source such as aquatic animals, like mussels and/or amphibia.
Biological adhesives are mostly peptide based adhesive materials adapted
to provide good adherence of biological tissue to other materials.
Especially preferred thereby are biological adhesives from aquatic
animals, since their adhesives are especially well adapted to a fluid
environment. Alternatively or additionally, the adhesive may also
comprise adhesive proteins from micro organisms, so called adhesins.
Adhesins are used by micro organisms to attach themselves to host cells
and therefore they show excellent adhesion qualities in an environment
such as a wound. Alternatively, more `classical` biological adhesives
such as fibrin may be used. One advantage of the wound closure material
of the present invention is that the amount of adhesive needed is
considerably reduced by the application of the adhesive as spots. This
leads to a reduction of costs for the material, since production and/or
isolation of biological adhesives tends to be rather expensive.

[0034] Alternatively, hybrid adhesives consisting of a synthetic backbone,
e.g. an acrylate, and biomimetic adhesives sites, e.g. polypeptides, may
also be used in place of the pure biological materials.

[0035] Preferably the at least one side of the core of biodegradable
material provided with the at least one spot of an adhesive is protected
from the environment before use, preferably by a release liner.
Especially in the case where there is the risk of premature curing of the
adhesive when in contact with the atmosphere, for example when moisture
curing polyurethanes are used, the side of the core bearing adhesive
spots has to be protected. Use of a release liner offers the advantage
that the protection can sequentially be removed from the wound closure
material thus keeping adhesive spots on other areas than the one being
used safe. Alternatively, the wound closure material may also be
protected from the environment by means of a protective case, pouch and
the like.

[0036] Another object of the present invention is to provide a method for
closing a wound. The method comprises the steps of: [0037] (a) applying
a wound closure material according to the present invention to a wound in
such a way that the at least two opposing sides provided with the at
least one discrete spot of an adhesive are facing at least two wound
edges; [0038] (b) pressing the at least two wound edges together with the
wound closure material in between the edges; and [0039] (c) allowing the
adhesive to cure so that the wound edges attach to the wound closure
material.

[0040] Since the wound closure material of the present invention is
provided with adhesive spots, there is enough space for tissue cells to
grow onto and/or into the wound closure material between the adhesive
spots. This has an advantageous effect on wound healing compared to cases
where the adhesive is applied onto the entire surface of the wound.
Moreover, compared to `classical` wound closure techniques using sutures
or the like, the wound closure material of the present invention serves
as scaffold for new tissue cells. The wound closure material of the
present invention may also act as artificial extracellular matrix for new
tissue cells.

[0041] A further objective of the present invention is to provide a method
of production of a wound closure material having improved wound healing
qualities. The production method comprises the steps of: [0042] (a)
providing a core of a biodegradable material having an open cell
structure [0043] (b) applying a multitude of spots of an adhesive to at
least one side of the core of biodegradable material, preferably by
screen printing.

[0044] The method of production may further comprise the step of applying
a removable protective sheet, preferably a release liner on the at least
one side of the core provided with the adhesive spots.

[0045] Preferably the spots are applied by screen printing technique in
step (b). Other techniques known in the art may also be used to apply the
spots of adhesive to the wound closure material.

[0046] Another objective of the present invention is to provide a method
of use of a wound filler material according to the present invention to
close a wound. As mentioned, the wound closure material of the present
invention provides improved wound healing qualities since the core
material may serve as scaffolding and/or artificial extracellular matrix
for new tissue cells. Moreover, since the adhesive is provided as
discrete spots there is enough space between the adhesive for tissue
cells to grow onto and/or into the core material without being hindered
by the adhesive material.

[0047] In a preferred embodiment the wound closure material of the present
invention is used to close a surgical transection. Compared to the
`classical` wound closure techniques, the wound closure material of the
present invention provides an easy to use and quick way of closing
transections. Moreover, the wound closure material of the present
invention offers improved wound healing properties compared to other
wound closure techniques.

[0048] Further advantages and characteristics of the present invention are
described in the following description of examples and figures.

[0049] FIG. 1: An exemplary embodiment of a wound closure material
according to the present invention.

[0050]FIG. 2: Three exemplary embodiments of different forms in which a
wound closure material according to the present invention may be
provided.

[0051] FIG. 1 shows an exemplary embodiment of the wound closure material
1 of the present invention. Wound closure material 1 comprises a core 2
of biodegradable material with an open cell structure. Core 2 is shown as
rectangular sheet. It is understood that core 2 might also be in any
suitable form, like pads, tapes and the like. The core 2 preferably
comprises a biodegradable polyurethane foam with an open pore structure
or a biodegradable non-woven fleece material. A first side 5 of the core
2 is provided with a multitude of spots 3 of an adhesive. The spots 3 are
shown as a pattern of rectangles distributed on the entire surface of the
first side 5. Spots 3 might also be provided in any suitable geometric
form, such as dots, circles, triangles and the like. The spots 3 might
also be distributed in another pattern or randomly. A second side 6
opposing the first side 5 is preferably also provided with spots 3 of an
adhesive. In such a case the wound closure material can be used to close
the edges of a wound together. Release liner 4 is provided on the first
side 5 to protect spots 3 from the environment, thus hindering premature
curing of the adhesive, e.g. due to moisture, and/or protecting the wound
closure material 1 of adhering to any objects.

[0052]FIG. 2 exemplarily shows three additional forms in which a wound
closure material of the present invention may be provided. Besides the
sheet form shown in FIG. 1, the core 2 of wound cover material 1 may also
be provided as rectangular or cylindrical pad. In the case of a
cylindrical pad, the spots 3 of adhesive are preferably provided on the
lateral surface. A third alternative is to provide the core 2 in the form
of a tape, preferably as roll 10. In this embodiment, the core 2 is
protected with release liner 4 to prevent sticking together of the core 2
when rolled up. The tape is preferably provided with spots 3 of adhesive
on both sides.